The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60-70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.
Animals ; Anticonvulsants/therapeutic use* ; Neurotoxins/pharmacology* ; Scorpion Venoms/pharmacology* ; Scorpions/chemistry* ; Voltage-Gated Sodium Channels

To evaluate the effectiveness and safety of Huachansu in the treatment of cancer-related pain,four Chinese databases( CNKI,VIP,Wan Fang,Sino Med) and three English databases( Cochrane Library,Medline,PubMed) were systematically and comprehensively retrieved since the establishment of each database to October 2018. Randomized controlled trials( RCTs) for the treatment of cancer-related pain with Huachansu were screened out according to pre-established inclusion criteria and exclusion criteria. Rev Man5. 3 software was used for Meta-analysis. A total of 241 articles were retrieved,and finally 10 studies were included. The total sample size was 1 293,including 648 in the experimental group and 645 in the control group. The overall quality of the included studies was generally low. The results of Meta-analysis showed that Huachansu combined with Western medicine acesodynes was superior to the single use of Western medicine acesodynes in the treatment of short-term pain relief,improvement of quality of life and reduction of constipation,nausea and vomiting,dizziness,drowsiness,anorexia and other adverse reactions. And it also has the advantage of a shorter onset time and longer duration time of analgesia,but cannot reduce the incidence of dysuria. Based on the findings,Huachansu had a certain effect in the treatment of cancer-related pain,and a significant positive effect on the improvement of quality of life and the reduction of adverse reactions. No serious adverse reactions occurred. However,due to the small number of studies included,the low quality of the included studies,published biases and other restrictions,the evidence in this study has a low quality,and the conclusion shall be adopted with caution. The effectiveness and safety of Huachansu in the treatment of cancer-related pain remained to be further confirmed in the future with a well-designed,rigorous,and standardized report,with a large sample size,multiple centers,and sufficient follow-up time for randomized controlled trials.
Amphibian Venoms ; therapeutic use ; Cancer Pain ; drug therapy ; Humans ; Quality of Life ; Randomized Controlled Trials as Topic

To systemically evaluate the efficacy and safety of Cinobufacini Injection in combination with platinum-contained first-line chemotherapy for treatment of non-small cell lung cancer(NSCLC). The randomized controlled trials(RCT) about the Cinobufacini in combination with platinum-contained first-line chemotherapy(versus chemotherapy alone) were collected through PubMed,Cochrane library,CNKI,VIP,CBM,and Wan Fang Database from database inception to December 2018. Two researchers extracted data and assessed the literature quality separately,and made a Meta-analysis by using Rev Man 5. 3 software. Twenty-seven RCTs were included in the present review,involving 2 125 patients,1 082 in treatment group and 1 043 in control group. The Meta-analysis results showed that as compared with chemotherapy alone,the combination of Cinobufacini and platinum-contained first-line chemotherapy could enhance one year survival rate(RR = 1. 34,95%CI[1. 17,1. 55],P< 0. 01),two year survival rate(RR = 1. 84,95% CI[1. 31,2. 59],P<0. 01),objective tumor response rate(RR = 1. 47,95%CI[1. 33,1. 63],P<0. 01); improve the quality of life for patients(RR =1. 54,95%CI[1. 37,1. 72],P < 0. 01); and reduce the incidences of WBC toxicity(RR = 0. 63,95% CI[0. 49,0. 80],P < 0. 01),platelet toxicity(RR = 0. 54,95%CI[0. 35,0. 84],P<0. 01),gastrointestinal reactions(RR = 0. 60,95%CI[0. 45,0. 80],P<0. 05),pain(RR = 1. 68,95% CI[1. 38,2. 03],P< 0. 01),and hair loss reaction(RR = 0. 76,95% CI[0. 59,0. 98],P < 0. 05). The results showed that for the treatment of NSCLC,the addition of cinofacini to conventional platinum-contained chemotherapy can increase the long-term and short-term efficacy of chemotherapy,improve the quality of life for patients,and reduce the side effects of platinumbased chemotherapy drugs. However,more high quality and large-scale randomized controlled trials are required to verify this conclusion in the future.
Amphibian Venoms/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Male ; Platinum/chemistry* ; Quality of Life

Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
Acupuncture Therapy ; Amphibian Venoms ; therapeutic use ; China ; Combined Modality Therapy ; standards ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Integrative Medicine ; standards ; Liver Neoplasms ; drug therapy ; pathology ; therapy ; Medicine, Chinese Traditional ; standards ; Neoplasm Staging ; Practice Guidelines as Topic

PURPOSE: Ocular manifestations in snake-bite injuries are quite rare. However, the unusual presentations, diagnosis and their management can pose challenges when they present to the ophthalmologist. Early detection of these treatable conditions can prevent visual loss in these patients who are systemically unstable and are unaware of their ocular condition. To address this, a study was conducted with the aim of identifying the various ocular manifestations of snake bite in a tertiary care center. METHODS: This is a one-year institute-based prospective study report of 12 snake bite victims admitted to a tertiary hospital with ocular manifestations between June 2013 to June 2014, which provides data about the demographic characteristics, clinical profiles, ocular manifestations, and their outcomes. RESULTS: Twelve cases of snake bite with ocular manifestations were included of which six were viper bites, three were cobra bites and three were unknown bites. Six patients presented with bilateral acute angle closure glaucoma (50%), two patients had anterior uveitis (16.6%) of which one patient had concomitant optic neuritis. One patient had exudative retinal detachment (8.3%), one patient had thrombocytopenia with subconjunctival hemorrhage (8.3%) and two patients had external ophthalmoplegia (16.6%). CONCLUSIONS: Bilateral angle closure glaucoma was the most common ocular manifestation followed by anterior uveitis and external ophthalmoplegia. Snake bite can result in significant ocular morbidity in a majority of patients but spontaneous recovery with anti-snake venom, steroids and conservative management results in good visual prognosis.
Acute Disease ; Adolescent ; Adult ; Animals ; Antivenins/therapeutic use ; *Elapidae ; Female ; Follow-Up Studies ; Glaucoma, Angle-Closure/diagnosis/*etiology/therapy ; Humans ; Male ; Middle Aged ; Ophthalmoplegia/diagnosis/*etiology/therapy ; Prospective Studies ; Snake Bites/*complications/diagnosis/therapy ; Snake Venoms/*poisoning ; Tertiary Healthcare ; Time Factors ; Uveitis, Anterior/diagnosis/*etiology/therapy ; *Viperidae ; Young Adult

OBJECTIVETo observe enhanced effects of polypeptide extract from scorpion venom (PESV) combined Rapamycin on autophagy of H22 hepatoma cells in mice and to explore its possible mechanism.

METHODSThe H22 hepatocarcinoma cell suspension was subcutaneously inoculated into 40 Kunming mice. Then tumor-bearing mice were randomly divided into four groups, i.e., the control group,the high dose PESV group, the low dose PESV group, and the combination group (high dose PESV + Rapamycin), 10 in each group. Mice in high and dose PESV groups were administered with 20 mg/kg and 10 mg/kg PESV respectively by gastrogavage. Mice in the combination group were administered with 2 mg/kg rapamycin and 20 mg/kg PESV by gastrogavage. The intervention lasted for 14 successive days. The tumor volume was measured once every other day, the tumor growth curve was drawn, and then the tumor inhibitory rate calculated. Pathological changes of the tumor tissue were observed by HE staining. Protein expression levels of mammal target of rapamycin (mTOR), UNC-51-like kinase-1 (ULK1), microtubule-associated protein1 light chain3 (MAPILC3A), and Beclin1 were detected by immunohistochemical assay.

RESULTSThe growth of H22 hepatoma transplantation tumor was inhibited in high and low dose PESV groups and the combination group (P < 0.05). And there was statistical difference in tumor weight and tumor volume between the combination group and high and low dose PESV groups (P < 0.05). There was no statistical difference in tumor weight or tumor volume between the high dose PESV group and the low dose PESV group (P > 0.05). lmmunohistochemical assay showed that the protein expression of mTOR was higher, but protein expressions of ULK1, MAP1LC3A, Beclin1 were lower in the control group than in the rest 3 groups (P < 0.05, P < 0.01). Compared with the high dose PESV group, protein expressions of ULK1, MAP1LC3A, and Beclin1 were obviously lower (P < 0.05).

CONCLUSIONPESV combined Rapamycin might inhibit the development of H22 hepatoma transplantation tumor in mice possibly through inhibiting the activity of mTOR, enhancing expressions of ULK1, MAP1LC3A, and Beclin1.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; therapeutic use ; Autophagy ; drug effects ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Liver Neoplasms ; Mice ; Neoplasm Transplantation ; Peptides ; Scorpion Venoms ; pharmacology ; therapeutic use ; Sirolimus ; pharmacology ; therapeutic use

BACKGROUNDNajanalgesin, a toxin isolated from the venom of Naja naja atra, has been shown to exert significant analgesic effects in a neuropathic pain model in rats. However, the molecular mechanism underlying this protective effect of najanalgesin is poorly understood. The present study sought to evaluate the intracellular signaling pathways that are involved in the antinociceptive effect of najanalgesin on neuropathic pain.

METHODSThe antinociceptive properties of najanalgesin were tested in hind paw withdrawal thresholds in response to mechanical stimulation. We analyzed the participation of the mitogen-activated protein kinase p38, extracellular-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) by western blot analysis. This inhibition of JNK was confirmed by immunohistochemistry.

RESULTSThe phosphorylation levels of JNK (as well as its downstream molecule c-Jun), p38, and ERK were significantly increased after injury. Najanalgesin only inhibited JNK and c-Jun phosphorylation but had no effect on either ERK or p38. This inhibition of JNK was confirmed by immunohistochemistry, which suggested that the antinociceptive effect of najanalgesin on spinal nerve ligation-induced neuropathic pain in rats is associated with JNK activation in the spinal cord.

CONCLUSIONThe antinociceptive effect of najanalgesin functions by inhibiting the JNK in a neuropathic pain model.

Animals ; Elapid Venoms ; therapeutic use ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Immunohistochemistry ; JNK Mitogen-Activated Protein Kinases ; genetics ; metabolism ; Male ; Neuralgia ; drug therapy ; enzymology ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

BACKGROUNDShoulder pain is a common complication of stroke. Bee venom acupuncture (BVA) is increasingly used in the treatment of post-stroke shoulder pain.

OBJECTIVETo summarize and evaluate evidence on the effectiveness of BVA in relieving shoulder pain after stroke.

SEARCH STRATEGYNine databases, namely MEDLINE, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), the Japan Science and Technology Information Aggregator, Electronic (J-STAGE), and four Korean medical databases, namely, the National Assembly Library, the Research Information Service System, the National Discovery for Science Leaders, and OASIS, were searched from their inception through August 2014 without language restrictions.

INCLUSION CRITERIARandomized controlled trials (RCTs) were included if BVA was used at acupoints as the sole treatment, or as an adjunct to other treatments, for shoulder pain after stroke.

DATA EXTRACTION AND ANALYSISTwo review authors independently selected trials for inclusion, assessed methodological quality and extracted data.

RESULTSA total of 138 potentially relevant articles were identified, 4 of which were RCTs that met our inclusion criteria. The quality of studies included was generally low, and a preponderance of positive results was demonstrated. All four trials reported favorable effects of BVA on shoulder pain after stroke. Two RCTs assessing the effects of BVA on post-stroke shoulder pain, as opposed to saline injections, were included in the meta-analysis. Pain was significantly lower for BVA than for saline injections (standardized mean difference on 10-cm visual analog scale: 1.46 cm, 95% CI=0.30-2.62, P=0.02, n=86) CONCLUSION: This review provided evidence suggesting that BVA is effective in relieving shoulder pain after stroke. However, further studies are needed to confirm the role of BVA in alleviating post-stroke shoulder pain. Future studies should be conducted with large samples and rigorous study designs.

Acupuncture Therapy ; methods ; Bee Venoms ; therapeutic use ; Humans ; Shoulder Pain ; therapy ; Treatment Outcome

OBJECTIVE: To evaluate the therapeutic effects of recombinant Exendin-4 and double-stranded adeno-associated virus (Exendin-4/dsAAV) on SD rats with type 2 diabetes (T2DM) through injecting it into submandibular gland (SG).
 METHODS: The Exendin-4/dsAAV was injected into submandibular gland of diabetic rat. The insulin and α-amylase were detected by real-time PCR at the 2nd, 4th and 8th weeks. The immunohistochemisty was used to detect the insulin contents in SG at the 8th week. The concentration of blood glucose and levels of insulin secretion were detected after pancreatectomy.
 RESULTS: The SG gland was bigger in Exendin-4/dsAAV group than that in the control group, but the changes in α-amylase were not significant. The Exendin-4 and insulin gene expression was increased in the Exendin-4/dsAAV group (P<0.05). The Exendin-4 and insulin were positive in the SG. The blood glucose was lower and insulin concentration was higher in the Exendin-4/dsAAV group than those in the control group after pancreatectomy (P<0.05), and the insulin content was also increased in the dsAAV groups.
 CONCLUSION Continuous expression of Exendin-4 in SG may improve glucose control and insulin secretion in T2DM rats through inducing expression of insulin.
Animals ; Blood Glucose ; analysis ; Dependovirus ; Diabetes Mellitus, Experimental ; therapy ; Diabetes Mellitus, Type 2 ; therapy ; Exenatide ; Genetic Therapy ; Injections ; Insulin ; chemistry ; Peptides ; genetics ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins ; genetics ; therapeutic use ; Submandibular Gland ; chemistry ; Venoms ; genetics ; therapeutic use ; alpha-Amylases ; chemistry

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Standard therapeutic approaches provide modest improvement in the progression-free and overall survival, necessitating the investigation of novel therapies. We review the standard treatment options for GBM and evaluate the results obtained in clinical trials for promising novel approaches, including the inhibition of angiogenesis, targeted approaches against molecular pathways, immunotherapies, and local treatment with low voltage electric fields.
Adult ; Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Bevacizumab ; Brain Neoplasms ; therapy ; Cancer Vaccines ; therapeutic use ; Electric Stimulation Therapy ; Glioblastoma ; therapy ; Humans ; Immunotherapy ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Snake Venoms ; therapeutic use ; Standard of Care ; Vaccines, Subunit ; therapeutic use